Saturday, November 29, 2014

Each day the NHS Choices team selects health stories that are making headlines. These, along with the scientific articles behind the stories, are sent to Bazian, a leading provider of evidence-based healthcare information. Bazian's clinicians and scientists analyse the research and produce impartial evidence-based assessments, which are edited and published by NHS Choices.

"Doctors call for tougher laws on alcohol abuse to tackle liver disease crisis," The Guardian reports. But this is just one of 10 recommendations for tackling the burden of liver disease published in a special report in The Lancet.

The report paints a grim picture of an emerging crisis in liver disease in the UK, saying it is one of the few countries in Europe where liver disease and deaths have actually increased rapidly over the last 30 years. It concludes with 10 recommendations to tackle the burden of liver disease.

The media has approached the recommendations from many different angles, with many sources only reporting on one, not all, of the recommendations.

For example, BBC News and The Daily Telegraph focused on the call for improved diagnosis in primary care: "GPs should offer liver scans to those who drink too much," reported The Telegraph.

The Guardian focused on calls for tougher regulation of the alcohol industry, such as minimum pricing for alcohol and a restriction on advertising and sponsorship by alcohol manufacturers, while the Mail's reporting focused on their core audience: "The middle class are fuelling an increase in death from liver disease".

What is liver disease?

There are more than 100 types of liver disease, which together affect at least 2 million people in the UK.

The report was compiled by a group of UK doctors and academics, and was published in the peer-reviewed medical journal, The Lancet.

The work was organised by The Lancet to "provide the strongest evidence base through the involvement of experts from a wide cross-section of disciplines, making firm recommendations to reduce the unacceptable premature mortality [death] and disease burden from avoidable causes, and to improve the standard of care for patients with liver disease in hospital".

The report stated that no people involved in the report were compensated for their time and no competing interests were declared.

The report involved many of the major medical and liver research councils in the UK, including the British Liver Trust, the Royal College of General Practitioners, the Children's Liver Disease Foundation, the Royal College of Physicians, the British Society of Gastroenterology, the Foundation for Liver Research, and the British Association for the Study of the Liver.

The views expressed in the report were described as those of the authors and do not necessarily represent the views of any of the organisations involved in this report.

What were the issues identified in the report?

The report outlined how liver disease in the UK "stands out as the one glaring exception" to the vast improvements in health and life expectancy made over the past 30 years for many diseases, such as stroke, heart disease and many cancers.

The rise in liver disease-related deaths was described as being linked to similar rises in known risk factors for liver disease, namely alcohol consumption, obesity and an increasing number of cases of viral hepatitis (especially hepatitis C).

Deficiencies in hospital and primary care of liver disease were also highlighted alongside the financial impact to the NHS.

Some of the key facts used to describe the current "crisis" in liver disease include: Death rates from liver disease have increased 400% since 1970 overall, and almost 500% in those under 65.

Liver disease is the third most common cause of premature death in the UK, and the rate of increase in liver disease is substantially higher in the UK than other countries in Western Europe. More than 1 million admissions to hospital per year are the result of alcohol-related disorders, and both the number of admissions and the increase in deaths closely parallel the rise in alcohol consumption in the UK over the past 30 years.

Of the 25% of the population now categorised as obese, most will have non-alcoholic fatty liver disease, and many (up to 1 in 20) will have ongoing inflammation and scarring that finally leads to cirrhosis. Of those patients with cirrhosis, 5-10% will get liver cancer.

This increasing burden of liver disease is added to by chronic viral hepatitis – annual deaths from hepatitis C have almost quadrupled since 1996, and about 75% of people infected are estimated to be still unrecognised. The same applies to chronic hepatitis B infection, which can progress to cirrhosis and liver cancer.

The cost to the UK's National Health Service is equally staggering, with estimates of £3.5 billion per year for alcohol-related health problems and £5.5 billion per year for the consequences of obesity. There is an unacceptable variation in the health outcomes of people attending different specialist liver disease services across the country. This means some specialist centres are performing much worse than others.

Based on survey data, the care of patients acutely sick with liver disease dying in hospital was judged to be good in less than half of cases. Other unacceptable findings were the inadequate facilities and lack of expertise of those caring for patients.

Deficiencies exist in primary care, which has crucial opportunities for the early diagnosis and prevention of progressive disease.

Those affected most by the burden of liver disease and death are the poorest and most vulnerable in our society.

What were the suggested solutions?

The report states the recommendations made were selected on the basis that they will have the greatest effect, and that these need to be implemented urgently.

"Although the recommendations are based mostly on data from England, they have wider application to the UK as a whole, and are in accord with the present strategy for healthcare policy by the Scottish Health Boards, the Health Department of Wales, and the Department of Health and Social Services in Northern Ireland."

The report's 10 most high-impact and urgently needed recommendations are:

1. Strengthen the detection of early liver disease and its treatment by improving the level of expertise and facilities in primary care.

2. Improve support services in the community setting for screening of high-risk patients.

3. Establish liver units in district general hospitals to be linked with 30 specialist centres distributed regionally to make highly specialised investigations and treatment available.

4. A national review of liver transplantation services to ensure better access for patients in specific areas of the country, and provide sufficient capacity for the anticipated increase in the availability of donor organs.

5. Strengthen the continuity of care in transition arrangements for the increasing number of children with liver disease surviving into adult life.

6. Implement a minimum price per unit, health warnings on alcohol packaging, and the restriction of alcohol advertising and alcohol sales.

7. The promotion of healthy lifestyles to reduce obesity in the country and its results on health, governmental regulations to reduce sugar content in food and drink, and the use of new diagnostic pathways to identify people with non-alcoholic fatty liver disease.

8. Eradicate infections from chronic hepatitis C virus in the UK by 2030 using antiviral drugs, reduce the burden of hepatitis B virus, target high-risk groups for these viruses, including immigrant communities, and use a universal six-in-one hepatitis B vaccination for infants.

9. Increase provision of medical and nursing training in hepatology, and wider educational opportunities for healthcare professionals to increase the number of doctors and nurses in hospitals and primary care.

10. Increase awareness of liver disease in the general population with a national campaign led by NHS England – clinical commissioning groups (CCGs) should increase awareness in area health teams.

Is the report reliable?

The report was an evidence-based piece combining established trend data and research evidence with expertise from various academics and doctors involved in liver disease and research.

It stresses the need for the recommendations to be evidence-based and scientifically focused. This gives us some confidence it is broadly reliable and represents the views of clinical opinion leaders and academics in liver disease research and treatment.

But, as far as we can tell, there was no systematic attempt to search and review the literature and data to ensure all relevant material was considered, as would be the case with a systematic review.

This means it is not clear to what extent evidence was used to support an existing stance, or whether certain relevant evidence or viewpoints have been intentionally or unintentionally excluded.

This leaves open the possibility that the report may present an overly critical or sensationalist view of the current state of affairs to stimulate a sense of urgency and instigate the action the authors perceive to be necessary.

But as the report used relatively objective data sources and stressed being scientifically focused, the impact of any bias is likely to be minimal.

What happens next? It is difficult to predict. Some of the recommendations, such as providing resources to make the early diagnosis of liver disease more likely, are purely clinical.

Whether or not the recommendation is taken up will probably be based on whether the resources are available and this can be justified.

But other recommendations – such as introducing minimal alcohol pricing, restricting alcohol sales to certain times of the day, and bringing in new rules regarding the advertising of alcohol – are politically controversial, and are likely to meet with fierce opposition from the alcohol industry.

It would be surprising if any party publically supported the recommendations this side of the upcoming general election.

Governments do have the power to change behaviour, which, as with the smoking ban, can prove very successful in achieving large-scale change.

But ultimately the responsibility of preventing liver disease is yours. If you moderate your alcohol consumption, try to maintain a healthy weight, and never share needles (if you are an injecting drug user), you should have a good chance of avoiding liver disease.

The initial daclatasvir NDA submitted by the company to the FDA focused on
the drug's use in combination with asunaprevir, an NS3/4A protease
inhibitor.

Given the withdrawal of asunaprevir by BMS in October, the FDA is requesting
additional data for daclatasvir in combination with other antiviral agents for
HCV treatment.

The company is currently in discussions with the US FDA about the scope of
these data.
Bristol-Myers Squibb executive vice-president and chief scientific officer
R&D Francis Cuss said: "Despite the recent advances in the treatment of
hepatitis C there remain significant areas of unmet high need in this disease
area.

"Our commitment remains to make daclatasvir-based regimens available to help
these difficult-to-treat patients achieve cure, and we will continue to
collaborate with the FDA to bring daclatasvir to patients in the US as quickly
as possible."

The company is dedicated to the ongoing clinical development program for
daclatasvir, which is currently being evaluated globally in multiple treatment
regimens for HCV patients with high unmet need.

The daclatasvir clinical trial program is focused on difficult-to-treat
patients, including pre- and post-liver transplant (ALLY-1), HCV patients
co-infected with HIV (ALLY-2) and patients with genotype 3 (ALLY-3)Source

U.S. regulators have declined to approve Bristol-Myers Squibb's daclatasvir as part of a combination hepatitis C treatment with another antiviral drug called asunaprevir.

The company said Wednesday that data it submitted to the Food and Drug Administration to win approval of daclatasvir focused on that drug's use with asunaprevir.

However, the New York-based drugmaker in October withdrew its application for approval of asunaprevir, citing "the rapidly evolving hepatitis C ... treatment landscape in the U.S." The FDA then requested more data on the effects of daclatasvir in combination with other drugs for treating hepatitis C, currently one of the hottest areas in drug research.

Bristol-Myers Squibb Co., which has a strong focus on drugs for viruses, cancer, heart disease and gene-related disorders, said it's now discussing with the FDA the scope of additional data needed.

Meanwhile, the company said it is committed to further testing of daclatasvir, part of a drug class called NS5A inhibitors. Multiple studies of the drug are being conducted around the world, including ones on patients who have had or are facing a liver transplant, and on patients who also have HIV.

"Despite the recent advances in the treatment of hepatitis C there remain significant areas of unmet high need," Francis Cuss, the company's head of research and development, said in a statement. "We will continue to collaborate with the FDA to bring daclatasvir to patients in the U.S. as quickly as possible."

Daclatasvir was approved in July in Japan for use in patients with one strain of the virus that's common in that country. It was approved in August in Europe for use along with other medicines in adult patients who have one of four strains of hepatitis C.

Multiple drugmakers have been trying to grab a piece of the hepatitis C drug market, given the millions of patients needing treatment for the liver-destroying virus and the ultra-high prices new drugs in the category are commanding.

Those include market leader Gilead Science Inc.'s Sovaldi and Harvoni. Their price tags ? $1,125-per-pill for the newest one, Harvoni ? have drawn criticism, but they spare patients the decades-old combination of months and months of antiviral pills and shots that cause flu-like side effects, yet barely cure half of patients.

I was living with hepatitis C for some 20 years before I was diagnosed in 2000, fortunately after undergoing a popular diet with man-made interferon, for some 48 weeks, I was cured! After my health was in check, my determination to remain healthy was fierce. I started dancing to the oldies in the morning, counting calories all day, and attempted yoga on weekends.

Eating Healthy
They say with age comes wisdom, today I find walking in the morning enjoyable, and following a non-diet approach to eating right - a relief. The Mediterranean way of eating has treated my liver well, maintaining a healthy weight is especially important if you have hepatitis C, the risk for developing scarring of the liver; fibrosis and cirrhosis is higher in people who are obese and living with the virus.

The Liver Changes As We Age
Naturally as we age the liver undergoes changes, for instance blood supply to the liver at age 60 in comparison to age 20 is reduced by 40 to 50 percent. The outcome of reduced blood supply to the liver affects its ability to regenerate, especially after toxic injury from drugs, alcohol or illness. Reduced blood flow can significantly affect metabolism as well, which may interfere with how some drugs are absorbed. These age-related changes in the liver can make monitoring medications we use difficult, leaving the liver more vulnerable to injury.

How Old Is Your Liver?
Recently a study at the University of California, Los Angeles (UCLA) investigated whether obesity is associated with accelerated liver aging. The researchers looked at close to 1,200 human tissue samples, 140 were liver samples. Body mass index (BMI) height and weight were noted as well. According to the results, biological age of the liver increased by 3.3 years, for every ten additional BMI units.

Lets Do The Math
As an example, I am five feet seven inches tall, and weigh 138, my BMI is 21.6. A women who is also the same height but weighs 202 would have a BMI of 31.6. According to the study, her liver is over three years older than mine. Maybe I'll skip the gravy and buttered veggies.

Mediterranean Diet
Over the years a vast amount of clinical research on the Mediterranean diet has demonstrated adhering to foods named in the diet may help reduce both liver fat, inflammation, and help protect against liver cancer. This month the BBC published an article on obesity naming the Mediterranean diet as a winner for reducing risk of heart attacks and strokes.

Fatty Liver And HCV
Today close to 30% of American adults have nonalcoholic fatty liver disease (NAFLD). In people living with hepatitis C it rises to around 40% and even higher in people with genotype 3. Often referred to in the medical world as HCV-induced steatosis, 60% to 80% people with genotype 3 have moderate or severe steatosis.

Insulin Resistance and Treatment Response
In the World J Gastroenterol, November 2014 issue, HCV and Insulin resistance is investigated, with an emphasis on treatment response in patients with different genotypes, in particular genotype 3. Additional information on treating HCV genotype 3 is available in HCV Advocates November newsletter.

Just For Fun

So What Happens When We Eat Too Much??

What Thanksgiving Dinner Does To Your BodyWith the average American consuming between 3,000 and 4,000 calories during Thanksgiving dinner, we look at what really happens to our bodies during this momentous feast, watch it here.

With all the research on liver disease, we know that obesity is associated directly with liver health. Following a healthy diet is beneficial in order to avoid additional liver related problems. Yes, maybe even during the holidays, I will be skipping that second piece of pie as well.

Stay healthy and happy all year long folks. Wishing you a cherished holiday.

The buildup of scar tissue, known as fibrosis, has a number of consequences, including inflammation and reduced blood and oxygen delivery to the organ. Long term, the scar tissue can lead to organ failure and sometimes eventually death. It is estimated that fibrosis contributes to 45 percent of all deaths in the developed world.

The researchers, led by Benjamin Humphreys, found that in mice, a rare population of stem cells located outside of blood vessels become myofibroblast cells that secrete proteins that cause scar tissue. Killing these stem cells prevents the deadly complications of fibrosis, the researchers report today in the journal Cell Stem Cell online. Rafael Kramann, a postdoctoral fellow in Humphreys’ lab, is the first author on the paper.

“Under normal circumstances, myofibroblasts stimulate wound healing, but when there’s an ongoing injury to an organ [such as the liver of a hepatitis C patient, the heart of a patient with high blood pressure, or the kidney of a patient with diabetes], these proteins clog up normal functioning,” said Humphreys, a Harvard Medical School associate professor at the Brigham, who leads the Harvard Stem Cell Institute Kidney Program.

The researchers are now in discussions with a pharmaceutical firm about screening for drugs that might target and shut off these fibrosis-causing stem cells in cases of chronic organ disease. The idea of using the stem cells as targets for drug discovery began with the formation — by Humphreys, Kramann, and Derek DiRocco — of MatriTarg Laboratories, the startup that won the 2013 Harvard Deans’ Health and Life Sciences Challenge.

“We wanted to know if eradication of this very small population of stem cells would improve organ function, and both kidney and heart were completely protected from developing fibrosis-related complications [such as kidney failure and heart failure],” said Humphreys, who also heads the Onco-Nephrology Program at the Dana-Farber Cancer Institute. “This provides an important proof of principle that drugs that target the stem cells could be therapeutic.”

The cellular origin of kidney fibrosis has long puzzled researchers. It was unknown which kinds of stem cells form myofibroblasts, and where these stem cells are located. One long-held hypothesis was that the stem cells that give rise to myofibroblasts are found in the bone marrow, but Humphreys’ research disproves that. By tagging a specific protein called Gli1 expressed by the myofibroblast-forming stem cells, the scientists showed that the cells are found on the periphery of blood vessels, and also reside within organs.

Humphreys does caution that the cell population his lab found is responsible for about 60 percent of all organ myofibroblasts, which means that they seem to be the most dominant source, but there may be other cells that also contribute to the myofibroblast population.

“We haven’t disproven every hypothesis, and our results do leave room for other cells that might contribute to fibrosis,” he said.

The Humphreys Lab collaborated with fellow Harvard Stem Cell Institute member Benjamin Ebert, an associate professor of medicine at Brigham and Women’s Hospital, on the work.

Sunday, November 23, 2014

THE long-awaited new Hepatitis C drug will be available on Spain’s national health system shortly, but only for certain patients.

According to Dr María Londoño from the Hospital Clínic in Barcelona, a member of the Spanish Agency for Medication and Healthcare Products, the drug Sovaldi will be administered to sufferers awaiting a liver transplant or who have undergone one, those with liver cirrhosis, or who have found more traditional treatment to have been ineffective.

Those with minor fibrosis – which accounts for the majority of Hepatitis C sufferers – will not be given the new drug.

“They will not be left untreated – they will be given other types of medication – but this is just a way of establishing which patients have the most urgent needs,” explains Dr Londoño.

Sovaldi is currently being given to patients with the most advanced conditions subject to authorisation from the Agency.

Spain’s health authority spent some months negotiating the price of Sovaldi, since the drug company manufacturing it wanted to charge prohibitive amounts for it which would mean huge restrictions on its administration.

Friday, November 21, 2014

Dara Gantly on the pressure to provide full access to powerful new treatments.

It is not often we hear the word ‘cure’ mentioned in the development of a new class of drug, but the direct-acting antiviral (DAAs) agents for people with the hepatitis C virus (HCV) have that exact potential. Indeed, this revolution in treatment could mean the ‘eradication’ for the condition. The only barrier to achieving this will be the ability to access and afford these new therapies. The ‘US$1,000 pill’ tagline has, as you might expect, caused quite a stir among healthcare funders and media alike, with some experts describing the costs of the drugs “as breathtaking as their effectiveness”.

Additional treatment options with high cure rates to be available to patients

The European Medicines Agency (EMA) has recommended a marketing authorisation for Exviera (dasabuvir) and Viekirax (ombitasvir + paritaprevir + ritonavir) for the treatment of chronic hepatitis C virus (HCV) infection in adults in combination with other medicinal products for the treatment of chronic hepatitis C.

HCV infection is a major European public health challenge. It affects between 0.4% and 3.5% of the population in different European Union (EU) Member States and is the most common single cause of liver transplantation in the EU.

Exviera and Viekirax belong to a new generation of medicines for chronic HCV infection that have high cure rates and have recently reshaped the way this disease is treated. Both Exviera and Viekirax block the action of proteins which are essential for HCV replication. Exviera targets the protein NS5B while Viekirax targets the proteins NS5A and NS3/4A.

This new generation of medicines allows cure of patients with chronic HCV infection without the need for interferons. Until recently, interferons were part of all treatment regimens for chronic HCV infection; these medicines can cause severe side effects that rule out their use in a considerable proportion of HCV patients.

Over the last year, the Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorisations for four new medicines for the treatment of HCV. In this area, the more treatment options that are available, the better chance a patient has to get the right treatment to cure the disease and to lead a longer and healthier life.

Both Exviera and Viekirax were evaluated under EMA’s accelerated assessment mechanism, a tool which aims to speed up patients’ access to new medicines where there is an unmet medical need.

For both medicines, the applicant received scientific advice from EMA in relation to quality, non-clinical and clinical aspects.

The opinion adopted by the CHMP at its November 2014 meeting is an intermediary step on Exviera and Viekirax’s path to patient access. The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State taking into account the potential role/use of this medicine in the context of the national health system of that country.

- Major regulatory milestone achieved toward approval in the European Union- Final decision from the European Commission expected in the first quarter of 2015

November 21, 2014: 08:00 AM ET

NORTH CHICAGO, Ill., Nov. 21, 2014 /PRNewswire/ -- The European Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted positive opinions for AbbVie's (NYSE: ABBV) investigational, all-oral, interferon-free treatment of VIEKIRAX™ (ombitasvir/paritaprevir/ritonavir) + EXVIERA™ (dasabuvir) with or without ribavirin (RBV) for patients with genotype 1 (GT1) and genotype 4 (GT4) chronic hepatitis C virus (HCV) infection. The European Commission will review the opinions and make a final decision sometime in the first quarter of 2015.

"The CHMP positive opinions mark an important milestone in our HCV development program and recognize the potential our treatment brings to people in Europe living with this chronic condition," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "Our treatment has been developed with the goal of achieving high cure rates in a broad range of genotype 1 patients with low rates of discontinuation and relapse."

The marketing authorization applications (MAAs) were submitted to the EMA on May 6, 2014 under an accelerated assessment, designated to new medicines of major public health interest. Review of the MAAs is being conducted under the centralized licensing procedure, which if approved will result in marketing authorizations valid in all 28 member states of the European Union, as well as Iceland, Liechtenstein and Norway.

Robust Clinical Program Supported Positive OpinionsThe CHMP opinions are supported by a robust clinical development program consisting of six pivotal Phase 3 studies (SAPPHIRE-I, SAPPHIRE-II, PEARL-II, PEARL-III, PEARL-IV and TURQUOISE-II)1,2,3,4,5 including more than 2,300 GT1 patients in over 25 countries. In addition, the positive opinions were supported by a Phase 2 study, PEARL-I, in GT4 patients without cirrhosis6, as well as preliminary data from the TURQUOISE-I study in GT1 HCV and HIV-1 co-infected patients7 and from the CORAL-I study in liver transplant recipients with recurrent GT1 HCV infection who were new to treatment after transplantation.8

Approximately nine million people in Europe are infected with HCV, which over time may lead to cirrhosis and liver failure in about 10-20 percent of people with chronic HCV.9,10 Genotype 1 is the most common type of HCV genotype9, accounting for 60 percent of cases worldwide.10 In Europe, the most prevalent genotype is 1b (47 percent).11 Genotype 4, most common in the Middle East, sub-Saharan Africa and Egypt, is becoming increasingly prevalent in several European countries including Italy, France, Greece and Spain.12

The U.S. Food and Drug Administration (FDA) granted priority review for AbbVie's treatment for patients with GT1 chronic HCV infection on June 13, 2014. AbbVie's treatment was also granted Breakthrough Therapy designation by the FDA, a status given to investigational treatments for serious or life-threatening conditions with preliminary clinical evidence demonstrating substantial improvement on at least one clinically significant endpoint compared to available therapy.

Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.

LAHORE: The Drug Regulatory Authority of Pakistan (DRAP) has finally fixed price of the ‘blockbuster’ oral drug – Sovaldi – after its registration in Pakistan, giving a good news to hepatitis C patients.

The decision was taken in a meeting of DRAP’s Drug Price Committee presided over by Pricing Director Mr Amanullah in Islamabad on Thursday, a senior official in the authority told Dawn.

He said the Ferozsons Laboratories is the sole company which was granted rights to sell and market this much-awaited drug in Pakistan at a price approximately Rs1,940 for each tablet. The company will make available a pack of 28 tablets for total price Rs55,000 after final approval by the federal government.

Some senior medical experts attending hepatitis C patients termed this development a major breakthrough, saying Pakistan was among a few countries where the chronic hepatitis C was alarmingly high and the patients were in dire need of this oral drug due to its surprisingly high success rate.

While highlighting the significance of the new life-saving drug, Technical Advisory Group (TAG) Member Prof Dr Ghiasun Nabi Tayab said presently approximately 10 million people in the country were living with chronic hepatitis C virus (HCV).

Of them, he said, seven million were in dire need of the new oral drug due to its above 80 per cent cure rate and almost ‘no side effects’ compared to the below 45 per cent success rate of the interferon injection therapy.

“Unfortunately, more than 280,000 new HCV patients were adding annually in Pakistan which was much disturbing for health mangers”, said Prof Tayab, who is also heading medicine department at Postgraduate Medical Institute (PGMI) in Lahore.

He said HCV infected patients were at risk of developing complications such as cirrhosis, hepatic encephalopathy, variceal bleed, hepatocellular carcinoma or liver related death.

On the other hand, unfortunately the liver transplant facility was also available only in one public sector health institute in Pakistan which was frustrating for the patients and their families.

About the Thursday’s development, the DRAP official said the American pharmaceutical company, Gilead Science, had produced this miracle drug in oral form last year for the treatment of chronic hepatitis C. The drug Sovaldi is available in the US market for $1000 for each tablet for the patients belonging to the elite class only.

It was later introduced in the international market and because of tremendously high demand of the oral drug, the company announced that the drug would be made available in the low-income countries on discounted price.

He said the DRAP, however, took one year to register and price it, ignoring the dire need the patients suffering because of the inordinate delay.

Earlier, the official said, the Gilead Science and the Ferozesons Laboratories had signed an agreement, under which the former would provide Sovaldi at a significant discount (98 % less than the US price) which was being termed a remarkable development for local patients.

The US company had recently finalised an accord with the Egypt, making available a tablet for approximately Rs8000 (in Pakistani currency) in the African country, which was much higher as compare to that for Pakistan. The hepatitis burden is enormously high in Egypt after Pakistan.

Before this development, the Sovaldi was being provided on the basis of the patient-to-patient strategy. As the doctors all over the country have started recommending the oral drug, the DRAP has been receiving requests from the patients for permission to import the same from the US.

The process of DRAP permission for the drug import to patients was taking minimum two months period. Presently, more than 3,000 patients’ applications from all over the country were pending with DRAP for permission to import the drug, the official said.

To a question, he said the new drug would be available in the local market shortly as the DRAP was going to move the case to the federal government within a week.

In just a few weeks, another pharmaceutical company will likely win FDA approval for a new drug to cure hepatitis C. That makes three breakthrough medications hitting the market in less than a year. It’s big news for the estimated twenty thousand Rhode Islanders – and many more throughout New England - living with chronic hepatitis C. Because some have been waiting decades for a cure.

That’s what has happened with hepatitis C. This virus slowly attacks the liver. It’s often 20 years or more before someone who’s infected notices anything wrong. Meanwhile, the infection scars the liver. And that could lead to cirrhosis or even liver cancer. Most of the estimated five million Americans who have chronic hepatitis C are somewhere on this spectrum of sickness right now.

By Kristin Gourlay
Providing medical assistance to low income Rhode Islanders will cost the state more than projected. One of the major factors behind the increase is the cost of two new drugs.

October 24

Opioid Addiction Crisis Fuels Another: Hep C
By Kristin Gourlay
Addiction usually leaves a wake of chaos, and all kinds of casualties - marriages, jobs, health. Most tragically, the current crisis of opioid addiction (to prescription painkillers and heroin) in Rhode Island has cost too many lives. Well over 160 Rhode Islanders have died from accidental opioid overdoses so far this year. Hundreds more might have joined them had it not been for the rescue drug naloxone.

This very moment, we’re standing at a crossroads. A place where two epidemics are about to meet. And what happens next is critical.

“The success we have over the next five to ten years is going to depend on what we do over the next one to two years.”

Meet Dr. John Ward. He oversees all things hepatitis C at the centers for disease control and prevention. And what he sees at this crossroads is a crisis.

“One, we have an epidemic of hepatitis c mortality. We have an increasing number of people dying from hepatitis c among the baby boom population who were infected decades ago.”About the series:

Hepatitis C infects an estimated five million Americans, though most of them don’t know it. But deaths from hepatitis C are on the rise in baby boomers. And throughout New England, new infections are creeping up among a younger generation. Less than a year ago, their only options for treatment were complicated regimens of injections that didn’t always lead to a cure. But brand new drugs could change everything. That is, if the cost doesn’t break us.

Updated November 20, 2014Reducing the cost of new hepatitis C drugs
Daclatasvir, Harvoni (ledipasvir/sofosbuvir) and Sovaldi.
An index of articles & research weighing the pros and cons over the high price of hepatitis C drugs.
The situation has Medicaid plans and insurers nationwide groping for the right balance. Worldwide patients are unable to afford treatment, while others wait in the wings on coverage...

Nov 20 (Reuters) - France has negotiated a big discount forGilead Sciences Inc's controversial new hepatitis C drug Sovaldi, under a government deal that ensures it will be fully reimbursable by health-funding schemes.

The Economic Committee for Health Products (CEPS) has fixed the price of a box of Sovaldi at 13,667 euros before tax, a reduction of 5,000 euros on the original price and "the lowest price in Europe", the Health Ministry said on Thursday.

Twelve weeks of treatment will now cost 41,000 euros ($51,373) before tax, against 56,000 euros previously.

In the United States, where Sovaldi's high price has sparked controversy and pushed up insurance companies' costs, a 12-week course costs $84,000, or $1,000 per pill.

Some 200,000 people in France have hepatitis C and the total cost of treatment to the national health fund is 800 million euros a year.

Sovaldi has racked up record sales despite a fierce debate over its price and concerns that high demand will place a huge burden on government-run health plans and private insurers.

Last month, U.S. regulators approved the sale of a new hepatitis C pill from Gilead, called Harvoni, which will cost $94,500 for an improved 12-week course of treatment to rid patients of the liver-destroying viral infection.

Harvoni has just won temporary approval for sale in France at 16,000 euros a box but negotiations are taking place with the French government aiming for a lower price. ($1 = 0.7981 euro)

Wednesday, November 19, 2014

Scientists at the Icahn School of Medicine at Mount Sinai (ISMMS) say recent research has shed light on the response of the hepatitis C virus (HCV) to targeted therapeutics and provided new insights about HCV’s role in cancer development. Their work (“Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors”), published in Nature Communications, focused on microRNA genes, a type of regulatory gene, and used whole-genome sequencing of the virus to challenge conventional wisdom about how the virus responds to emerging therapies.

Their findings, note the researchers, may contribute to more effective development of hepatitis C drugs in the future and to more personalized treatment for patients.

According to the Centers for Disease Control and Prevention, HCV is widespread, affecting some 3% of the world’s population and more than 3 million people in the United States alone. Recent CDC reports indicate that hepatitis C infections are on the rise among young people and are increasingly the cause of death among baby boomers.

The vast majority of people who get HCV will suffer chronic infection, which can lead to liver inflammation, cirrhosis, and liver cancer. Highly effective new treatments have been launched recently, but their high prices have caused public outcry and limited widespread use. There is no commercially available vaccine for hepatitis C.

In this new study, Mount Sinai researchers examined HCV response to an experimental treatment that targets and blocks the supply of a microRNA (miR-122) that the virus needs for infection of human cells. Contrary to expectations, they found that depleting the supply of miR-122 could trigger drug resistance with the emergence of HCV strains able to infect cells with negligible levels of the microRNA. This information could be used for more effective dosing of drugs targeting this gene, as well as for pre-treatment analysis to determine which patients may respond best to this class of drugs.

“This effort, which was made possible by innovative microRNA analysis, offers significant progress toward precision medicine in treating HCV patients,” said Matthew Evans, Ph.D., assistant professor of microbiology at the ISMMS and a co-author of the study. “There is a critical need for more weapons in our arsenal to fight HCV, particularly for affordable, effective treatment as we try to stay a step ahead of this virus and prevent it from developing the kind of drug resistance we’re seeing in the bacterial realm.”

In another key finding, the scientists uncovered knowledge that may help answer the longstanding question of how HCV leads to cancer. The study demonstrated that HCV hijacks the miR-122 gene, diminishing its normal activity in liver cells. Since this microRNA is known to be a potent tumor repressor, it is possible that HCV robs cells of their natural defenses against uncontrolled growth. Such an outcome could contribute to cancers that arise from chronic HCV infection.

“We found that HCV itself reduces miR-122’s activity in the cell, possibly through binding and sequestering miR-122,” wrote the investigators. “Our study provides insight into the interaction between miR-122 and HCV, including viral adaptation to reduced miR-122 bioavailability, and has implications for the development of anti-miR-122-based HCV drugs.”

“Our study offers broader implications for this class of microRNA genes and their interaction with targets, which may be useful for a number of diseases in addition to hepatitis C,” said Brian Brown, Ph.D., associate professor of genetics and genomic sciences at the ISMMS and a co-author of the study. “We are also intrigued by this new information that may shed light on the link between HCV and the onset of cancer and look forward to future efforts to explore this theory.”

The Dirty Side of Soap Triclosan, a common antimicrobial in personal hygiene products, causes liver fibrosis and cancer in mice.

Triclosan is an antimicrobial commonly found in soaps, shampoos, toothpastes and many other household items. Despite its widespread use, researchers at University of California, San Diego School of Medicine report potentially serious consequences of long-term exposure to the chemical.

The study, published Nov. 17 by Proceedings of the National Academy of Sciences, shows that triclosan causes liver fibrosis and cancer in laboratory mice through molecular mechanisms that are also relevant in humans.

Triclosan is an antimicrobial additive found in many liquid hand soaps and other household products. Image source: Arlington County

“Triclosan’s increasing detection in environmental samples and its increasingly broad use in consumer products may overcome its moderate benefit and present a very real risk of liver toxicity for people, as it does in mice, particularly when combined with other compounds with similar action,” said Robert H. Tukey, PhD, professor in the departments of Chemistry and Biochemistry and Pharmacology. Tukey led the study, together with Bruce D. Hammock, PhD, professor at University of California, Davis. Both Tukey and Hammock are directors of National Institute of Environmental Health Sciences (NIEHS) Superfund Programs at their respective campuses.

Tukey, Hammock and their teams, including Mei-Fei Yueh, PhD, found that triclosan disrupted liver integrity and compromised liver function in mouse models. Mice exposed to triclosan for six months (roughly equivalent to 18 human years) were more susceptible to chemical-induced liver tumors. Their tumors were also larger and more frequent than in mice not exposed to triclosan.

The study suggests triclosan may do its damage by interfering with the constitutive androstane receptor, a protein responsible for detoxifying (clearing away) foreign chemicals in the body. To compensate for this stress, liver cells proliferate and turn fibrotic over time. Repeated triclosan exposure and continued liver fibrosis eventually promote tumor formation.

Triclosan is perhaps the most ubiquitous consumer antibacterial. Studies have found traces in 97 percent of breast milk samples from lactating women and in the urine of nearly 75 percent of people tested. Triclosan is also common in the environment: It is one of the seven most frequently detected compounds in streams across the United States.

“We could reduce most human and environmental exposures by eliminating uses of triclosan that are high volume, but of low benefit, such as inclusion in liquid hand soaps,” Hammock said. “Yet we could also for now retain uses shown to have health value — as in toothpaste, where the amount used is small.”

Triclosan is already under scrutiny by the FDA, thanks to its widespread use and recent reports that it can disrupt hormones and impair muscle contraction.

It is a drug that cures hepatitis C in 90 per cent of cases and was considered ground-breaking when it came on to the market.

Manufactured by Gilead, Sofosbuvir was licenced for use late last year. And in April this year, NHS England took the unusual step of setting up a special access scheme so patients with less than a year to live were able to be treated without waiting for the National Insitute for Health and Care Excellence (Nice) to evaluate whether it should become routinely available on the NHS.

But it is expensive – £35,000 for a 12 week course. So now NHS England is balking at the potential cost. In fact so much so, this programme has learned that they have asked Nice to delay implementation.

This, liver specialists say, will put patients’ lives at risk. Estimates are that every month’s delay could lead to 40 people with hepatitis C developing preventable cancer, and 30 patients progressing to a severe form of cirrhosis.

Nice is due to finish its final assessment in January. It is usual for them to give the NHS three months to find the money or put staff – if needed – in place. NHS England is thought to have asked them to delay this by six months.

It is already in the public domain that NHS England fears that it could end up cost £1bn if it was provided to 20,000 patients. A leaked letter to the Health Service Journal described this as prohibitive.

Professor William Rosenberg, a consultant hepatologist at the Royal Free Hospital in London, said this was wrong on two counts.

“Not everybody is going to come forward. In the UK we have only detected half of the cases of hepatitis C in the country and we have treated way less than half of those. So we are not going to get a deluge of patients coming forward.

“Secondly, under the early access scheme, NHS England has worked very effectively with the 15 centres delivering this care to, in effect, ration therapy to the patients with the greatest need. We could continue to do that.

“I feel absolutely distraught for the patients who can see that these treatments are available throughout the world and are provided on the continent. You just go across the Channel, ​patients could get access to these treatments. They’re life-saving, and yet they cannot get them in this country,” he said.

The argument regularly put forward by doctors is that while it may have a hefty price tag, it is a drug that cures. That means no treatment for liver cancer, or liver transplants which can cost £100,000 alone.

And as the Hepatitis C Trust says, that also mean lives not lost and people who can go back to work and pay taxes.

“What this does is prevent the need for a huge amount of expense later on by treating and curing now,” Charles Gore, the trust’s chief executive, said.

Tonight NHS England said it would now continue to make the drug available for patients with liver failure until the Nice assessment. But it would not comment on what happens beyond that.Follow @vsmacdonald on Twitter
- See more here

Of Interest
Updated November 19, 2014Reducing the cost of new hepatitis C drugsDaclatasvir, Harvoni (ledipasvir/sofosbuvir) and Sovaldi.An index of articles & research weighing the pros and cons over the high price of hepatitis C drugs.The situation has Medicaid plans and insurers nationwide groping for the right balance. Worldwide patients are unable to afford treatment, while others wait in the wings on coverage.

European Commission Grants Marketing Authorization for Gilead's Harvoni(Ledipasvir/Sofosbuvir), the First Single Tablet Regimen to Treat the Majority of Chronic Hepatitis C Patients With Genotype 1 and 4 ‏

-- Once-Daily Single Tablet Regimen Eliminates the Need for Interferon and Ribavirin for Patients with Genotype 1 and 4 Hepatitis C without Cirrhosis or with Compensated Cirrhosis --

FOSTER CITY, Calif.--(BUSINESS WIRE)--Nov. 18, 2014-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the European Commission has granted marketing authorization for Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg), the first once-daily single tablet regimen to treat the majority of chronic hepatitis C genotype 1 and 4 infection in adults. Harvoni combines the NS5A inhibitor ledipasvir (LDV) with the nucleotide analog polymerase inhibitor sofosbuvir (SOF), approved by the European Commission under the tradename Sovaldi® in January 2014.

Harvoni is indicated for the treatment of chronic hepatitis C virus (HCV) in adults and is recommended in treatment-naïve and treatment-experienced cirrhotic and non-cirrhotic genotype 1 and 4 patients with a treatment duration of 12 or 24 weeks depending on prior treatment history and cirrhosis status. Eight weeks of treatment with Harvoni may be considered in non-cirrhotic treatment-naïve genotype 1 patients. In genotype 1 and 4 patients with decompensated cirrhosis, and genotype 3 patients with cirrhosis and/or prior treatment failure, Harvoni should be used in combination with ribavirin for 24 weeks. Harvoni is also indicated for patients with HCV who have HIV co-infection.

Today's marketing authorization is based on the clinical development program that included more than 2,000 patients with HCV infection, and follows an accelerated assessment by the European Medicines Agency, a designation that is granted to new medicines of major public health interest. It allows for the marketing of Harvoni in all 28 countries of the European Union (EU).

"Genotype 1 patients living with hepatitis C in Europe and the physicians who treat them have been waiting for a treatment advance like this for decades," said Graham Foster, MD, Professor of Hepatology, Queen Mary University of London. "With Harvoni, we have the potential to transform the way we treat people living with the most prevalent form of hepatitis C in Europe. We can now expect very high SVR rates, and for many patients, we can eliminate the need for interferon injections and ribavirin and offer a cure in a once-daily tablet."

The marketing authorization is supported primarily by data from three Phase 3 studies, ION-1, ION-2 and ION-3. These studies evaluated eight, 12 or 24 weeks of treatment with Harvoni, with or without ribavirin, among nearly 2,000 genotype 1 HCV patients with compensated liver disease.

These studies included non-cirrhotic treatment-naïve patients (ION-3), cirrhotic and non-cirrhotic treatment-naïve patients (ION-1) and cirrhotic and non-cirrhotic patients who failed prior therapy with an interferon-based regimen, including regimens containing an HCV protease inhibitor (ION-2). The primary endpoint for each study was sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV. In these studies, ribavirin was not shown to increase response rates. Trial participants in the ribavirin-free arms (n=1,080) achieved SVR12 rates of 94 to 99 percent.

The approval was also supported by preliminary data from the SOLAR-1 trial, which evaluated difficult to treat patients with decompensated cirrhosis and patients who have undergone liver transplantation, and from the ERADICATE trial, which evaluated genotype 1 HCV patients co-infected with HIV. The primary endpoint in these studies was SVR12. At the time of submission, only preliminary results were available. In the SOLAR-1 trial, participants with decompensated cirrhosis receiving a 12-week treatment regimen of Harvoni plus ribavirin had an SVR4 rate of 90 percent (n=45/50). In post-liver transplant patients without decompensated liver disease, SVR4 rates were greater than 95 percent (n=109). In an interim analysis of the ERADICATE trial, 40 of the 50 patients had reached 12 weeks post treatment and had SVR12 rates of 98 percent (n=39/40).

In these clinical studies, fatigue and headache were more common in patients treated with Harvoni compared to placebo.

Harvoni was approved by the U.S. Food and Drug Administration and Health Canada in October 2014 and in New Zealand in November 2014. Regulatory submissions for Harvoni are pending in Japan and Switzerland. Sovaldi as a single agent is approved for use in the European Union and in the United States, Canada, Australia, New Zealand, Egypt, Switzerland and Turkey.

Important Safety Information

The summary of product characteristics of co-prescribed medicinal products should be consulted before starting therapy with Harvoni.

Harvoni should not be administered concomitantly with other medicinal products containing sofosbuvir.

In clinical studies, fatigue and headache were more common in patients treated with Harvoni compared to placebo.

Contraindications include hypersensitivity to the active substances or to any of the excipients. Co-administration with rosuvastatin or St. John's wort (Hypericum perforatum) is contraindicated. Co-administration with certain P-glycoprotein (P-gp) inducers (e.g. rifampicin, carbamazepine and phenytoin) is not recommended. Monitoring of digoxin and dabigatran is recommended when used with Harvoni. Caution and frequent renal monitoring is recommended for co-administration with certain HIV antiretroviral regimens. Safety has not been established in patients with severe renal impairment. For patients on statins dose reduction should be considered and careful monitoring for statin adverse events (myopathy and rhabdomyolysis) should be undertaken. A Summary of Product Characteristics is available at www.ema.europa.eu.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that physicians and patients may not see advantages of Harvoni over other therapies and may therefore be reluctant to prescribe the product, and the risk that private and public payers may be reluctant to provide coverage or reimbursement for the product. Further, additional studies of Harvoni may produce unfavorable results. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended September 30, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

Harvoni and Sovaldi are registered trademarks of Gilead Sciences, Inc., or its related companies

For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at +1 (650) 574-3000.

Open up the floodgates: Gilead's ($GILD) hep C wonder-cocktail, Harvoni, has won approval in Europe.With cure rates as high as 99.1%, analysts expect the drug--which combines Sovaldi with NS5A inhibitor ledipasvir--to outstrip solo Sovaldi as the fastest-growing drug of all time. And the EMA's green light, which grants Gilead marketing authorization in the EU's 28 countries, is certainly a necessary step if Harvoni--which won FDA approval this October--wants to live up to those forecasts.

"Genotype 1 patients living with hepatitis C in Europe and the physicians who treat them have been waiting for a treatment advance like this for decades," Graham Foster, a hepatology professor at London's Queen Mary University, said in a statement. "With Harvoni, we have the potential to transform the way we treat people living with the most prevalent form of hepatitis C in Europe."

This is the second installment in a four-part series.
LOS ANGELES (MarketWatch) -- Look around the health-care world, and the almighty dollar can rear its head just about anywhere.

It’s often seen in the balance sheets of biopharmaceutical giants, where net margins are double or even triple that of a normal, healthy corporation. Finance gets injected into the medical system when doctors are able to charge triple what Medicare’s fees are by staying out of public health programs and keeping their true expenses under wraps....

Karen Ignagni, chief executive of America’s Health Insurance Plans, the industry’s trade group, has frequently criticized the pricing on Sovaldi, saying it is putting a significant burden on insurance carriers. She worries that more specialty drugs like Sovaldi are scheduled to start coming through the pipeline in coming years via what she calls the “opaque wall of innovation.”
“The question is, what are we paying for?” she said....

Monday, November 17, 2014

An Ottawa woman’s death has intensified a conversation about whether provinces should be responsible for funding a costly hepatitis C medication.

Brenda Peever died on Nov. 4 after struggling with complications from hepatitis C. Now, her daughter, Jennifer, is speaking out about the family’s three-year fight to fund life-saving treatment.

Jennifer Peever says her family’s saga started when her mother contracted hepatitis C after receiving a tainted blood transfusion. Peever’s mother was later identified as a candidate for an effective -- but unaffordable -- drug.

Note that a trial of a three-drug direct-acting drug regimen against HCV revealed that a short course was associated with some degree of sustained virologic response, but did not perform as well as longer courses.

Another trial of combination direct acting therapy found that SVR rates were very high even without the addition of ribavirin.

BOSTON -- A new study suggests that some subgroups of patients with hepatitis C (HCV) infection can achieve sustained virologic responses (SVR) in as short as 4 weeks using an aggressive, investigational three-drug regimen, researchers reported here.

In the 4-week duration part of a multi-arm clinical trial, all 31 non-cirrhotic genotype 1 HCV-infected patients achieved undetectable virus at follow-up week 2. according to Eric Lawitz, MD, of the Texas Liver Institute in San Antonio.

Among the 30 patients treated for 6 weeks, all reached undetectable virus by follow-up week two, but four of those patients later relapsed, giving an 86.7% SVR at week 8.
"This is a phase II study. This is a proof of principle that we can accomplish SVR at 8 weeks," Lawitz told MedPage Today. "This was the first time there was a planned 4-week duration trial. Even though there were a number of relapses, it is biologically plausible to cure a very select subset of patients at 4 weeks."

The researchers conducting the so-called C-SWIFT trial also looked at 6-week and 8-week courses of treatment for harder-to-cure cirrhotic genotype 1 HCV patients.

"Cirrhotics had SVR of about 95% at 8 weeks," Lawitz said. He noted that all 102 patients in the study -- cirrhotics and non-cirrhotics -- achieved undetectable virus by follow-up week two. Among the cirrhotic patients, four patients out of 20 who were treated for 6 weeks relapsed. There was one relapse among the 21 cirrhotic patients treated for 8 weeks.

"There are some valuable lessons learned from this," Lawitz said. "It is encouraging to see a three-drug regimen achieve a 95% SVR at 8 weeks in the setting of cirrhosis. It shows we may be able to get to an 8-week regimen for all patient types.

"Our study looks at short duration therapy," Lawitz said. The registration trial for the two investigative agents will show SVR12 results. "In the C-SWIFT trial, which is ongoing, we used a three-drug regimen of grazoprevir and elbasvir -- the investigative drugs -- and sofosbuvir, which is already on the market."

"What we saw at the end of 4 weeks was that all but six patients had achieved undetectable virus, but by follow-up week two those six patients went on to be undetectable, so at follow-up week two there was 100% of patients that were undetectable." he said.

"In the 6-week arm, all but one patient was negative at the end of the treatment and that patient also went on to become negative by follow-up week two. In the cirrhotic arms all patients were undetectable at either 6 or 8 weeks," he said.

Lawitz said the three-drug regimen was well-tolerated with few serious adverse events occurring in any treatment regimen, possibly a factor of the short treatment duration.

In commenting on the research, press conference moderator Michael Fried, MD, director of the University of North Carolina Liver Center, Chapel Hill, told MedPage Today, "I agree that this is a very important study because it does sort of set the limits of where we might be able to go with these drugs in terms of duration of therapy.

"Everyone is sort of focused on shorter duration of therapy, and perhaps we can identify certain subgroups that may be able to get treated for 4 weeks, but it certainly will require a lot more research in that area."

The patients in the C-SWIFT study were in their 50s and more than 60% of each arm of the trial were men. More than 75% of the patients were diagnosed with genotype 1a. Lawitz said the overall study also includes patients diagnosed with genotype 3 hepatitis C virus infection, but the results from that group will be reported at a later meeting.

Meanwhile, the same drugs, but without sofosbuvir, appeared to allow difficult to treat HCV patients to attain a sustained virologic response with or without the addition of ribavirin, Lawitz reported in a separate presentation.

The C-WORTHY was a randomized, dose response, parallel-group, multiple-site, double-blind clinical trial comparing diverse patient populations exposed to different durations of treatment of grazoprevir/elbasvir with or without ribavirin in patients with chronic hepatitis C virus infection.
In C-WORTHY Parts A and B which were presented at AASLD, 471 patients with chronic hepatitis C virus genotype 1 infection were enrolled and randomized. The research was published online in The Lancet simultaneously with presentation at the meeting.
At the meeting, Lawitz reported:

28 of 31 cirrhotic patients naïve to antiviral therapy – 90% -- treated for 12 weeks with the fixed dose combination of grazoprevir 100 mg plus elbasvir 50 mg once daily plus ribavirin achieved the goal of sustained virologic response at 12 weeks (SVR12). There were two late relapses in this group.

28 of 29 similar patients –97% -- treated for 12 weeks with the dual investigative drug without ribavirin achieved SVR12. There was one relapse.

31 of 32 similar patients – 97% -- treated for 18 weeks with all 3 drugs achieved SVR12. There were no relapses in this group.

29 of 31 similar patients – 94% -- treated for 18 weeks without ribavirin achieved SVR12. There were two relapses.

30 of 32 null responders with or without cirrhosis – 94% -- treated for 12 weeks with the three drugs achieved SVR12. There were no relapses.

30 of 33 similar patients –91% -- treated for 12 weeks with the two investigational drugs achieved SVR12. There were three relapses in this group.

33 or 33 null responders with or without cirrhosis –100% -- treated for 18 weeks with all three drugs achieved SVR12. There were no relapses.

31 of 32 similar patients – 97% -- treated with the two investigational drugs for 18 weeks achieved SVR12. There were no relapses.

"High efficacy was observed regardless of the presence or absence of ribavirin or extended treatment duration from 12 weeks to 18 weeks," Lawitz said in his oral presentation during a special hepatitis plenary session at the annual meeting of the American Association for the Study of Liver Diseases..

Session moderator Anna Lok, MD, of the University of Michigan in Ann Arbor, told MedPage Today, "The data are impressive."

The combination is "is going through Phase III clinical trials so we will have to see what those results look like. If the Phase II results are confirmed, the treatment will be approved," Lok said.

"I don't think we can say that one regimen will be superior to another, but it is comparable to other treatments we have seen. That means that we have more choices. If we have more choices then maybe the prices will come down a bit through competition. That's what we all hope."

The treatment naïve patients in the study arms were about 58 years old; the treatment experienced null responders were about 54 years of age. There were more men than women in the study and more than 90% of the patients in the study arms were white. Almost all the patients in the treatment naïve population had cirrhosis (one patient did not). About 35% of patients who were null responders had cirrhosis.

Adverse events were infrequent. Lawitz said the treatment was well-tolerated. He noted that more adverse events were noted when ribavirin was added to the treatment regimen.

Merck plans to submit the New Drug Application to the FDA for grazoprevir/elbasvir in 2015.

TORONTO, Nov. 17, 2014 /CNW/ - An estimated 250,000 Canadians live with hepatitis C, a deadly virus that attacks the liver and can lead to liver cancer, liver failure or even death. A new survey conducted by Ipsos Reid on behalf of the Canadian Liver Foundation (CLF) found that among adults born between 1945 and 1975, only 29 per cent believe their own age group has the most people living with hepatitis C. Yet, adults born between 1945 and 1975 have the highest risk of having undiagnosed hepatitis C. The survey also found more than 75 per cent of the respondents have not been tested for the deadly disease or don't know if they have.

"One in five people with the virus don't know they are living with hepatitis C because symptoms often don't appear until it's too late and the liver is damaged," said Dr. Morris Sherman, Chairperson for the Canadian Liver Foundation and hepatologist at Toronto General Hospital. "We want to encourage all those who are at risk to get tested and urge those who have been tested to speak to their doctor about treatment."

Adults born between 1945 and 1975 (including those born in Canada or abroad) are a high risk group because they may have undergone blood transfusions before testing of blood was introduced, experienced medical procedures or immunization before modern infection control measures became the norm (especially outside of Canada) or experimented with intravenous drug use (even once). The disease is spread through blood to blood contact with an infected person or through unsterilized equipment, such as tattoo or piercing needles, that have been contaminated with infected blood.

52 year old Sharon Rider contracted hepatitis C at age 16 when she received a transfusion during back surgery to correct her scoliosis. She was finally diagnosed 23 years later when she underwent a battery of blood tests prior to a second back surgery.

"When I found out I was terrified that I might have passed it on to my husband or children," said Sharon. "No one had ever suggested that I should get tested for hepatitis C and I didn't have any symptoms that would have suggested that this virus was attacking and damaging my liver."

The national survey of more than 1,000 Canadians found that although the 1945 to 1975 age bracket do not realize they are at such a high risk, the majority of respondents (86 per cent) have heard of hepatitis C and 77 per cent know that the liver is the most affected organ. In addition, 60 per centunderstand that you can have the virus and not know it. However, only 11 per cent believe the disease has the highest rates of premature death among a list of diseases. Left untreated, hepatitis C progresses to cirrhosis, liver cancer or liver failure and can result in death.

In 2012, the Canadian Liver Foundation recommended that adults born between 1945 and 1975 undergo a one-time test for hepatitis C. This recommendation was supported by a Canadian Medical Association Journal article in which authors suggested that wide-spread testing of this age group could identify as many as 77% of those who are infected.

Among the survey respondents, the most motivating reason to get tested is a recommendation from a doctor (70 per cent), followed by realizing you have a risk factor (44 per cent).

"Family physicians and other front line health care professionals have a vital role to play in educating their patients about risk factors and encouraging hepatitis C testing," said Dr. Sherman. "Without diagnosis and timely treatment, individuals who are living unknowingly with hepatitis C will continue to progress toward more severe liver damage and risk suffering the most severe consequences of this disease."

Numbers by region:
Almost 40 per cent of survey respondents in Atlantic and Quebec do not know that getting a tattoo can put them at risk of contracting hepatitis C.

Only 61 per cent of those in Quebec believe that hepatitis C can lead to the most life-threatening consequences including cirrhosis, liver cancer, liver transplant and death.
Only 10 per cent of respondents in Ontario and Quebec believe that hepatitis C causes the highest rate of premature death from a list of other infectious diseases.

72 per cent of Ontario respondents and 76 per cent of BC respondents have not been tested or do not know if they have been tested for hepatitis C.

CLF will participate in a legislative education day on November 20th at Parliament Hill in Ottawa. The education day will aim to inform politicians on the toll hepatitis C is taking on Canadians.

To determine your risk of contracting hepatitis C and to learn more about hepatitis C testing, please visit liver.ca/hepcinfo.

About the Canadian Liver Foundation

Founded in 1969 by a group of doctors and business leaders concerned about the increasing incidence of liver disease, the Canadian Liver Foundation (CLF) was the first organization in the world devoted to providing support for research and education into the causes, diagnoses, prevention and treatment of all liver disease. Through its chapters across the country, the CLF strives to promote liver health, improve public awareness and understanding of liver disease, raise funds for research and provide support to individuals affected by liver disease.

HCV Education
Review learning activities, editorials, with new data about interferon-free regimens approved for HCV, as well as investigational drugs still in the pipeline. Links are provided to support, patient friendly information, clinical trials, peer-reviewed journals, videos, conferences with commentary, all updated on a continuous basis.

Users can search for a hepatitis C clinical trial by category (genotype), or learn how to evaluate a clinical trial and become familiar with commonly used terms. HCV Advocate offers an easy to navigate HCV Medications Blog as well, organized by HCV genotype

View each rebuttal and all ongoing media coverage. In June the HCV community was blindsided when an article with a somewhat "clickbait" headline was released by The Guardian. The Guardian reported on a systematic review published by the Cochrane Collaboration that suggested achieving SVR (cure) for patients using hepatitis C direct-acting antivirals (DAAs) doesn't correlate with any long term benefits.

The controversy over expensive new drugs for hepatitis C
Link to research and news articles addressing the high cost of hepatitis C drugs; insurance restrictions - private insurers/Medicaid - and availability of generic versions/India, Egypt and other lower-income countries or through online "buyers clubs"

Liver Cancer After Treatment For Hepatitis C
​Research demonstrates that while SVR markedly reduced liver-related complications and liver cancer, some long-term risk for liver cancer remained in those who were cured of Hepatitis C. But after direct-acting antiviral therapy does the risk of developing liver cancer increase?

Meeting Updates

April 19-23
The European Association for the Study of the Liver (EASL) International Liver Congress (ILC 2017)

Merck today announced its strategic decision to discontinue the development of the investigational combination regimens MK-3682B (grazoprevir/ruzasvir/ uprifosbuvir) and MK-3682C (ruzasvir/uprifosbuvir) for the treatment of chronic hepatitis C virus (HCV) infection. This decision was made based on a review of available Phase 2 efficacy data and in consideration of the evolving marketplace and the growing number of treatment options available for patients with chronic HCV infection

Two HCV Drugs to Be Discontinued
The Food and Drug Administration (FDA) announced that Rebetol(ribavirin; Merck) capsules and PegIntron (peginterferon alfa-2b; Merck) for Injection are being discontinued. The decision is business-related and not due to safety or efficacy issues with the drugs.

Rebetol is a nucleoside analogue indicated for chronic hepatitis C in combination with interferon alfa-2b (pegylated and nonpegylated), in patients ≥3 years of age with compensated liver disease. It is supplied as 200mg capsules in 56-, 70-, and 84-count bottles. The Rebetol discontinuation is effective February 1, 2016.
PegIntron is an antiviral indicated for treatment of chronic hepatitis C in patients with compensated liver disease. It is supplied as 50mcg/0.5mL, 80mcg/0.5mL, 120mcg/0.5mL, and 150mcg/0.5mL single-use vials and single-use pre-filled pens. No effective date is available for the PegIntron discontinuation.

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